Kawachi Y, Arai K, Moroda T, Kawamura T, Umezu H, Naito M, Ohtsuka K, Hasegawa K, Takahashi-Iwanaga H, Iwanaga T
Department of Immunology, Niigata University School of Medicine, Japan.
Eur J Immunol. 1995 Dec;25(12):3452-9. doi: 10.1002/eji.1830251237.
Extrathymic T cells exist in the liver and are often seen in close contact with Kupffer cells in the hepatic sinusoids. Since selective depletion of Kupffer cells has become possible by using liposome-encapsulated clodronate, it was investigated whether elimination of Kupffer cells influences the level of extrathymic T cells in the liver. Extrathymic T cells were identified as interleukin-2 receptor beta-chain (IL-2R beta) intermediate TCR (TCRint) cells by two-color staining for CD3 or T cell receptor (TCR) and IL-2R beta. The elimination of Kupffer cells did not significantly affect levels of TCRint cells up to 7 days after treatment. We then examined monocyte colony stimulating factor (M-CSF)-deficient op/op mice (low levels of Kupffer cells). Extrathymic T cells both in the liver and spleen of these mice were detected at a level comparable to that of control mice. Since extrathymic T cells in the liver are sometimes located in the parenchymal space, the relationship between extrathymic T cells and hepatocytes was then examined. Electron microscopy revealed that some hepatic T cells adhered directly to hepatocytes. When hepatocytes were damaged by a single injection of CCl4, hepatocyte death and subsequent hepatic fibrosis were induced. Beginning 3 days after injection, CD3int cells, but not other type of cells, decreased prominently. Purified CD3int cells, as well as whole lymphocytes in the liver, were cytotoxic against syngeneic hepatoma. In parallel with the above-mentioned hepatic damage, the cytotoxic activity of lymphocytes against such targets was impaired in the liver. These results suggest that extra-thymic generation of TCRint cells and their acquisition of cytotoxic function are relatively independent of Kupffer cells, but are dependent on hepatocytes.
胸腺外T细胞存在于肝脏中，且常在肝血窦中与库普弗细胞紧密接触。由于使用脂质体包裹的氯膦酸盐已能够选择性清除库普弗细胞，因此研究了清除库普弗细胞是否会影响肝脏中胸腺外T细胞的水平。通过对CD3或T细胞受体（TCR）与白细胞介素-2受体β链（IL-2Rβ）进行双色染色，将胸腺外T细胞鉴定为IL-2Rβ中等水平的TCR（TCRint）细胞。在治疗后长达7天的时间里，清除库普弗细胞并未显著影响TCRint细胞的水平。然后，我们检查了单核细胞集落刺激因子（M-CSF）缺陷的op/op小鼠（库普弗细胞水平较低）。在这些小鼠的肝脏和脾脏中检测到的胸腺外T细胞水平与对照小鼠相当。由于肝脏中的胸腺外T细胞有时位于实质间隙，因此随后研究了胸腺外T细胞与肝细胞之间的关系。电子显微镜显示，一些肝T细胞直接粘附于肝细胞。当单次注射四氯化碳使肝细胞受损时，会诱导肝细胞死亡及随后的肝纤维化。在注射后3天开始，CD3int细胞显著减少，而其他类型的细胞则没有。纯化的CD3int细胞以及肝脏中的全淋巴细胞对同基因肝癌具有细胞毒性。与上述肝损伤同时，肝脏中淋巴细胞对此类靶标的细胞毒性活性受损。这些结果表明，TCRint细胞的胸腺外生成及其细胞毒性功能的获得相对独立于库普弗细胞，但依赖于肝细胞。
